Pilocarpine, its polyuronic acid salts, nitrate, as well as other salts, are known to be useful in the treatment of glaucoma, a symptomatic condition often characterized by elevated intraocular pressure. U.S. Application Ser. No. 553,399 filed Feb. 26, 1975, now abandoned, discloses and claims amorphous dipilocarpinium pamoate. Although this amorphous salt is useful in glaucoma therapy (e.g., extends duration of ocular hypotensive activity relative to that observed with previously described pilocarpine salts), its amorphous nature presents a drawback in not being readily and easily handleable, in being difficult to formulate in an appropriate ocular delivery system and in being difficult to generate stoichiometrically. We have found that crystalline dipilocarpinium pamoate readily overcomes the present difficulties encountered with the amorphous material.
The amorphous dipilocarpinium pamoate as disclosed in said application is prepared by a technique well known in the art for preparing salts. For example, pilocarpine and pamoic acid are suspended in an aqueous medium and the salt thus prepared is isolated by removal of water. This technique, however, leads to an oily material which must be placed in an oven to obtain solid dipilocarpinium pamoate. The salt thus obtained, however, is amorphous and not crystalline; in addition, one cannot be certain that the ratio of pilocarpine to pamoic acid will be 2:1.
We have found a novel process for preparing crystalline dipilocarpinium pamoate employing unique conditions which lead to substantially pure dipilocarpinium pamoate having a ratio of 2:1 of pilocarpine to pamoic acid.